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S2 E1 KCU COB > E1 Immunology > Flashcards

E1 Immunology Flashcards

1
Q

P- Selectins are found on _____, and its ligand is ____.

It assists migration into ____

A

P- Selectins are found on Endothelium, and its ligand is Sialyl Lewis Ag.

It assists migration into Peripheral

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2
Q

P-selectins are activated on endothelium cells by:

A

Histamine and Thrombin released by mast cells and macrophages

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3
Q

E- Selectins are found on _____, and its ligand is ____.

It assists migration into ____

A

E- Selectins are found on Endothelium, and its ligand is Sialyl Lewis X Ag

It assists migration into Peripheral

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4
Q

E-Selectins are activated by

A

Cytokines: TNF and IL-1

Secreted by macrophages and mast cells

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5
Q

L- Selectins are found on _____, and its ligand is ____.

It assists migration into ____

A

L- Selectins are found on NEUTROPHILS, MONOCYTES, T-CELLS, AND B-CELLS, and its ligand is SIALYL LEWIS X AG.

It assists migration into SECONDARY LYMPH NODES VIA HEV

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6
Q

What type of receptor is LFA-1

What expresses it?

What is its ligand?

A

Integrin

Neutrophils, monocytes, All T-Cells, Naive B-Cells

(Leukocytes and Lymyphocytes)

ICAM-1 and ICAM-2

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7
Q

What type of receptor is Mac-1

What expresses it?

What is its ligand?

A

Integrin

Neutrophils, monocytes, dendritic cells (Leukocytes)

ICAM-1 and ICAM-2

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8
Q

What type of receptor is VLA-4

What expresses it?

What is its ligand?

A

Integrin

Monocytes and all T-Cells

VCAM-1

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9
Q

What type of receptor is Alpha(4)Beta(7)

What expresses it?

What is its ligand?

A

Integrin

Monocytes, T-Cells, B-Cells

VCAM-1 and MadCAM-1

(mucosal addressin cell adhesion molecule-1)

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10
Q

How is an integrin activated?

A
  • Integrins are activated in all leukocytes when chemokines bind to their receptors
    • They bind as they are rolling along endothelial surface
    • Induces a conformational change in the extracellular domain
    • Conformational change leads to increased affinity
    • Bent is low-affinity conformation
    • Extended is high-affinity conformation
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11
Q

What are the 4 families of chemokines?

What is the determining feature in each one?

A
  • C Chemokines: Single Cysteine
  • CC or ß Chemokines: Two Cysteine residues are adjacent
  • CXC or Alpha Chemokines: Cysteine residues are separated by an AA
  • CX3C chemokines: Two cysteines are separated by three amino acids
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12
Q

What is CCL2 and its function?

A

A CC Chemokine

Original Name: MCP-1

Major function: Mixed Leukocyte recruitment in transmigration of leukocytes (Monocytes)

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13
Q

What is CXCL8 and its function?

A

A CXC Chemokine

Original name IL-8

Function: Neutrophil Recruitment in transmigration of leukocytes

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14
Q

Where do dendritic cells go to present an Ag to a Naive T-cell?

How does it get there?

A

Lymph Nodes

AFFERENT lymphatic vessels

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15
Q

How is a Naive T-cell activated in the lymph nodes?

Once activated, what does it do?

A

Dendritic Cell presents an Ag to it

Activated T-Cells will leave the Lymph node via the EFFERENT lymphatic vessel

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16
Q

Where are HEV found?

(High Endothelial Venules)

A

Only in the Lymph Nodes

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17
Q

Where are P and E selectins found?

Where are their ligands found?

A

Endothelial surfaces

Leukocytes

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18
Q

Where are L-Selectins found?

Where are their ligands found?

A

On the Lymphocytes

On the endothelial cell

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19
Q

What is an addressin?

A

An adhesion molecule found on HEV

Assists in the binding and migration of lymphocytes into lymph nodes

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20
Q

What is CCL19 and its function?

A

CC Chemokine

Original Name: MIP-3ß

Function: T cell and dendritic cell migration into parafollicular zones of LYMPH NODES

Found on HEV

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21
Q

What is CCL21 and its function?

A

CC Chemokine

Original Name: SLC

T cell and dendritic cell migration into parafollicular zones of lymph nodes

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22
Q

What prevents T-Cells from leaving the lymph node?

A

In the blood, S1PR1 receptors are internalized because they bind to the S1P ligands. Once they enter the lymph node, there is no S1P ligand, but the S1PR1 receptors are tied up with the S1P that they were originally bound to.

T-Cells naive or activated cannot leave for hours to days until the S1PR1 receptor resurfaces and recognizes the S1P gradient

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23
Q

What is CCL4 and its function?

A

CC Chemokine

Original name: MIP-1ß

Function: T-cell, dendritic cell, monocyte, and NK Recruitment

Used in homing

It is also an HIV coreceptor

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24
Q

What is CXCL10 and its function?

A

A CXC Chemokine

Original Name: IP-10

Function: Effector T-Cell Recruitment

In T-Cell homing

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25
Q

What is CXCL12 and its function?

A

CXC Chemokine

Original name: SDF-11åß

Function: homing of naïve B cells to LNs

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26
Q

What is CSCL13 and its function?

A

CXC Chemokine

Original name: BCA-1

Function: B-cell migration into follicles; T follicular helper cell migration into follicles

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27
Q

What are the circulating effector cells in innate immunity?

A

Neutrophils: Early phagocytosis and killing of microbes

Macrophages: Phagocytosis and killing of microbes; Secretes cytokines and stimulate inflammation

NK Cells: Lysis of cells, activation of Macrophages

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28
Q

What are the circulating effector proteins in innate immunity?

A

Complement: Killing of microbes, opsonization of microbes, activation of leukocytes

Mannose-binding lectin (collecting): Opsonization of microbes, activation of complement (lectin pathway

C-Reactive Protein (pentraxin): Opsonization of microbes, activation of complement

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29
Q

What cytokines of the innate immune system are involved in inflammation?

A

TNF, IL-1, Chemokines

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30
Q

What cytokines are involved in resistance to viral infection of the innate immune system?

A

IFN-a and IFN-ß

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31
Q

What cytokines are involved in Macrophage activation of the innate immune system?

A

IFN-y

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32
Q

What cytokines are involved in IFN-y production by NK cells and T-cells of the innate immune system?

A

IL-12

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33
Q

What cytokines are involved in the proliferation of NK cells of the innate immune system?

A

IL-15

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34
Q

What cytokines are involved in the control of inflammation of the innate immune system?

A

IL-10 and TGF-ß

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35
Q

What are the steps in PRR-Triggered responses Phagocytes

A
  1. Phagocytes use PRR to recognize self from non-self
  2. Recognition of fMet on prokaryotes

(fMet is not found on eukaryotes)

  1. Polymorphonuclear cells bind proteins that start with fMet
  2. Use those protein attached cells to control motility and initiate phagocytosis
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36
Q

What are the roles of TLR’s?

A

Toll-like receptors

Recognize foreign materials

Also activates inflammation

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37
Q

What are the cell surface TLR’s and what do they recognize?

A

TL-1-2-4-5- and -6

Recognize extracellular microbes

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38
Q

What TLR’s are found on endosomes and what do they recognize?

A

TLR -3-7-8- and -9

Nucleic acids

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39
Q

Receptor TLR1: TLR2 Heterodimer

A

Binds to Lipopeptides and GPI

Found on Monocytes, dendritic cells, eosinophils, basophils, and mast cells

Located on the plasma Membrane

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40
Q

Receptor: TLR2: TLR6 Heterodimer

A

Binds to Lipoteichoic acid or Zymosan

Found on Monocytes, dendritic cells, eosinophils, basophils, and mast cells

Located on the plasma membrane

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41
Q

Receptor TLR3

A

Binds to Double-stranded viral RNA

Found on NK Cells

Located on Endosomes

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42
Q

Receptor: TLR4:TLR4 Homodimer

A

Binds to Lipopolysaccharide

Found on Macrophages, dendritic cells, mast cells, and eosinophils

Located on the plasma membrane

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43
Q

Receptor TLR5

A

Binds to Flagellin

Found on intestinal epithelium

Located on the plasma membrane

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44
Q

Receptor TLR7

A

Binds to Single Stranded viral RNA’s

Found in Plasmacytoid dendritic cells, NK cells, eosinophils, and B cells

Located on endosomes

45
Q

Receptor TLR8

A

Binds to Single Stranded viral RNAs

Found in NK cells

Located on endosomes

46
Q

Receptor TLR9

A

Binds to Unmethlylated CpG-Rich DNA

Found in Plasmacytoid dendritic cells, B Cells, eosinophils, and basophils

Located on endosomes

47
Q

Receptors TLR10 Homodimer and heterodimers with TLR1 and 2

A

Binds to: Unknown

Found on Plasmacytoid dendritic cells, basophils, eosinophils, and B cells

Located in: Unknown

48
Q

What adaptor proteins are associated with TLR3?

A

TRIF is the only adaptor protein used to activate NF-kB and IRFs transcription factors

NF-kB: Nuclear factor-kB

IRF: INterferon regulatory factors

49
Q

What adaptor proteins are used by TLR4?

A

TLR4 uses both MyD88 and TRIF to activate NF-kb and IRFs transcription proteins

50
Q

What adaptor proteins are used by TLRs 1,2,5,6,7,8 and 9?

A

TLRs 1,2,5,6,7,8 and 9 us MyD88 to activate transcription factors NF-kB and IRF

51
Q

What are NLR’s and their functions?

A

NOD-Like Receptors

Controls the activation of inflammatory responses

Act as scaffolding proteins that signal for NF-kB and MAPk signaling pathways

52
Q

How is an Inflammasome activated and what pathway does it initiate?

A
  • Activated when NLR recognizes cytosolic PAMPS and DAMPS
    • Can be microbial, crystals, or reduced potassium concentrations
  • Activates Caspase-1 which lead to the secretion of IL-1ß and IL-18
  • Also leads to Pryroptosis:
    • Programmed cell death of macrophages and dendritic cells
      • Releases inflammatory mediators
        • IL-1ß, IL-18, TNF, IL-6, and IL-8
53
Q

What is Pyroptosis and its effects?

A

Programmed cell death of macrophages and dendritic cells

Cell death leads to the release of inflammatory mediators:

IL-1ß

IL-18

TNF

IL-6

IL-8

54
Q

What are Scavenger Receptors and their functions?

A

Scavenger Receptors are found on macrophages that mediate recognition and initiate phagocytosis of microorganisms

They recognize PAMPs

They bind negative charges of LPS, Liptoteichoic acid, nucleic acids, ß-glucans and proteins from foreign pathogens

55
Q

What domain does lectin receptors posses and recognize?

A

Carbohydrates recognition domain

Carbohydrates: microbial mannose, N-acetylglucosamine, and ß-glucans

NB! Compare: Eukaryotic cell carbohydrates are most often terminated by galactose and sialic acid

56
Q

What are eukaryotic cell carbohydrates most often terminate by?

A

Galactose and sialic acid

57
Q

What are the Lectins functions?

A

Facilitate phagocytosis of macrophages and dendritic cells, secrete cytokines to initiate adaptive immunity

Soluble mannose-binding lectin (MBL) is involved in complement activation via the lectin pathway

58
Q

What are the 5 components of inflammation?

A
  1. Increased in blood supply to the affected area
    1. Leads to redness and heat
  2. Increased capillary permeability
    1. Leads to leaks from the blood vessels
    2. Swelling and pain
  3. Massive influx of neutrophils in the tissues
  4. Arrival of monocytes and macrophages (16-48 hours)
  5. Distortion of the homeostasis and loss of function
59
Q

What is HMGB1?

A

A DAMP secreted from necrosis.

Activates the NF-kB pathway

RAGE is its receptor

60
Q

What is Uric Acid?

A

A DAMP that induces the transcription of NF-kB

61
Q

What are HSPs?

A

A DAMP that induces NF-kB pathway

Induce release of inflammatory cytokines: TNF-alpha and IL-1ß

62
Q

What are defensins?

Where are they found?

What do they do?

A

Small cationic peptides with a cationic region and a hydrophobic region

Made by epithelial cells of mucosal surfaces and by granule-containing leukocytes

Directly toxic to microbes (bacteria, fungi, and enveloped viruses)

They insert and disrupt their membranes

63
Q

What are Cathe’licidins?

Where are they found?

What do they do?

A

Antimicrobial peptides

Found in neutrophils and barrier epithelia of skin, GI, and respiratory

They can be directly toxic to microbes and activate leukocytes

They can also be antiinflammatory by binding to DNA and preventing Inflammasome activation

64
Q

Are natural killer T-cells part of adaptive or innate immunity?

A

Innate

65
Q

KARS vs KIRS

What are they?

What do each do?

What determines if a cell dies

A

Activating Receptors (Killer cell Ig-like receptor) vs Inhibitory Receptors

Recognizes: Stress molecules (MICA and MICB) vs Class I MHC

KARS: Will lead to protein kinases that will activate proteins to kill the host cell

KIRS: Sufficient binding will lead sparing of the target cell

Insufficient binding will lead to killing of the host cell

66
Q

Steps of NK cells killing target

A
  1. NK cell releases perforins which polymerize and form a hole in the target cell
  2. Granzymes from NK enter perforin hole and degrade enemy enzyme
  3. Host cell dies by apoptosis
  4. Macrophages engulfs and digest dying cell
67
Q

What is a zymogen?

How does it relate to the complement cascade?

A

An inactive precursor enzyme

It is altered to become an active protease that will cleave the next complement protein in the cascade

68
Q

Describe the role of C3 Convertase in the complement pathway

A

C3 Convertase will cleave C3 to produce C3a and C3b

C3a: Chemoattractant for neutrophils and stimulates inflammation

C3b: Binds to microbial surface as an opsonin to promote phagocytosis

C3 Convertase + C3b = C5 Convertase

Used in the next step of complement

69
Q

Describe the role of C5 Convertase in the complement pathway

A

Cleaves C5 to produce C5a and C5b

C5a: is a chemoattractant for neutrophils and also induces changes in the permeability of blood vessels

C5b: Attaches to the bacterial surfaces and initiates the MAC Complex

70
Q

What role does the MAC complex play in the complement cascade?

A

Creates a hole in the membrane that leads to bacterial leakage and lysis

71
Q

How is MAC made in the complement system?

A
  1. C6 and C7 bind to C5b to form a complex (C7 is what allows it to bind to the bacterial membrane)
  2. C8 binds to the complex and inserts itself on to the membrane
  3. C5bC6C7C8 complex is used to allow the polymerization of 1-16 C9 molecules to form the pore
    (The pore is made of C9 molecules that were allowed to be formed because of the C5bC6C7C8 complex)
72
Q

What allows the activation of the alternative complement pathway?

A

The creation of C3b via

a. “tickover” of C3 (spontaneous degradation)
b. Positive feedback from the creation of C3 convertase complex with C3bBb and C3 convertase
c. C3b produced from Classical or Lectin Pathway

73
Q

How is C3b used in the alternative complement pathway?

A
  1. C3b binds to Factor B
  2. Factor B is cleaved into Bb and Ba via Factor D
  3. C3b binds to Bb and becomes a C3 Convertase
    ​Creates C3bBb Convertase that will cleave more C3 to create positive feedback
    ** Side note** Properdin binds to the C3bBb convertase to stabilize it
    *** Binding of another C3b will create a C5 Convertase
74
Q

What stabilizes the C3bBb Convertase complex in the alternative pathway?

A

Properdin

75
Q

What is the function of MBL in the Lectin complement pathway?

A

It is the receptor that recognizes the glycoproteins and glycolipids on the cell surfaces of microbes

When it binds, it activates MASP1 and MASP2: Which is similar to the C1r and C1s Components of the Classical Pathway

(Mannose-associated serine proteases)

76
Q

What is the role of MASP1 and MASP2?

What complement pathway do they belong to?

A

They are part of the Lectin Complement Pathway

They are mannose associated serine proteases

They cleave C2 and C4 to create C4bC2a.

C4bC2a is a C3 Convertase

77
Q

What is DAF?

A

A complement regulatory protein that blocks the interaction between C2:C4b

Also promotes the disassociation of the C3 complex: C4bC2a

78
Q

What is CR1?

A

A complement regulatory protein

Promotes the disassociation of the C3 convertase: C4bC2a

(Complement receptor 1 also serves as a cofactor for Factor I)

79
Q

What is the role of Factor 1?

A

Uses cofactor CR1

Will prevent the assembly of C3 and C5 convertases

80
Q

Role of C5a

A

Recruitment of leukocytes

Change the permeability of blood vessels

(Plays a role in the complement pathway)

81
Q

Role of C3a

A

Stimulates inflammation

Recruitment of leukocytes

(Plays a role in the complement pathway)

82
Q

Role of C3b

A

Opsinin that is involved in recognition of microbe by phagocyte

Also involved in the creation of multiple C5 convertases

(Plays a role in the complement pathway)

83
Q

What cells do C3a, C4a, and C5a activate?

A

Mast Cells, basophils, neutrophils, monocytes, and macrophages

(leukocytes)

84
Q

What role do mast cells and basophils have in inflammation?

A

They release vasoactive substances

85
Q

What role do neutrophils have in inflammation?

A

They increase chemokinesis, release prostaglandins, and utilize ROS and RNS

86
Q

What role do monocytes and macrophages have in inflammation

A

They release IL-1 and IL-6, prostaglandins, and ROS and RNS

87
Q

What are the inflammatory effects of soluble complement fragments?

A

Contraction of smooth muscles

Increased permeability of blood vessels

Degranulation of basophils

Chemotaxis, release of NOS and lysosomal enzymes

(All stimulated by C3a, C4a, but mainly C5a)

(**Note C4a hardly does any because their receptors are rarely found)

88
Q

What are the steps of phagocytosis and the killing of the microbes?

A
  1. Complement activation leads to depositions of C3b on the bacterial cell surfaces
  2. Cr1 on macrophages recognize it and bind to the bacterium
  3. Endocytosis begins
  4. Macrophage membranes fuse creating a phagosome with the bacteria inside
  5. Phagosome fuses with the lysosome to create a phagolysosome
    1. Contains ROS, NOS, and proteolytic enzymes that will degrade it
89
Q

What can bacteria express that will prevent the killing of the bacteria in the phagolysosome?

A

Catalase

Will neutralize the hydrogen peroxide which would have been used by myeloperoxidases to create hydroxide and chlorine that will destroy the cells

90
Q

What are collectins?

A

Pattern Recognition Receptors (PRRs) that contain lectin heads

Used in innate immunity

91
Q

What are Pulmonary Surfactant proteins SP-A and SPD?

What is their role?

A

Collectins with PRRs

They can act as opsinins (for phagocytosis), inhibit bacterial growth, and activate macrophages

Found in the lungs

92
Q

What are Filocins?

A

Plasma proteins that are used in the humoral innate immune system

They are PRRs that recognize carbohydrates:

N-acetylglucosamine and N-acetyl

They will opsonize for phagocyte recognition and activate lectin complement vias MASPs

93
Q

What induces acute inflammation and promote the expression of IL-6?

A

TNF and IL-1

94
Q

What are the shared effects of TNF, IL-6, and IL-1?

A

Mediate protective systemic effects of inflammation

Induction of fever, acute phase proteins by the liver, and leukocytosis (production of leukocytes)

95
Q

What are the negative side effects of TNF

A

Decreased cardiac output

Thrombosis and capillary leak

Metabolic abnormalities due to insulin resistance

All of which can lead to septic shock

96
Q

What are CRP and SAP?

A

Acute phase protein s

97
Q

What can CRP and SAP do?

A

Recognize and phosphorylcholine and phosphatidylethanolamine respectively

Can activate classical complement pathway by binding to C1q

98
Q

What are the properties of Abs

(7 of them)

A

Immunomodulation

Reduce damage to host from an inflammatory response

Organized T-Cell response

Opsonization

Activation of complement (Classical)

Toxin Neutralization

Direct antibody antibacterial activity

99
Q

What are the chains and domains of the Ab structure?

A

Light Chain and Heavy Chain

Variable Domain: Ag Binding domain

Constant Domain: Determines the type of Ab

100
Q

Papain’s function

A

Cleaves IgG into two Fab fragments and an Fc fragment

Fab Fragments: Fragment ag-binding

Fc: Fragment crystallized

101
Q

What is the role of pepsin

A

Proteolysis that breaks IgG into a bivalent fragment ag-binding fragment (F(ab)2) and a degraded peptide fragment

102
Q

What are the 5 types of heavy chains and their corresponding Ig__?

A

Mu, delta, gamma, epsilon, and alpha

IgM, IgD, IgG, IgE and IgA

103
Q

What is the reason that IgM is membrane-bound?

A

compared to IgG which has a tail region, it has an extra CH4 domain that anchors it to the plasma membrane

104
Q

In which types of foreign materials is high affinity binding of the ab most crucial?

A

Toxins and viruses

105
Q

What is valence and how does it apply to Ab binding?

A

Valence is how many Ags an Ab can bind to

(I.e. IgG has two binding sites: Therefore, valence =2)

Having two or more binding sites for an Ag can dramatically increase the tightness of binding

106
Q

What is avidity?

A

Avidity is the overall strength of binding between Ag-Ab

107
Q

What are the two factors that avidity is dependent on?

A

Affinity of the Ab for a SINGLE epitope

AND

Valence fo BOTH Ab and Ag

108
Q
A

S2 E1 KCU COB (5 decks)

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